DNA methylation in CHO cells

•An introduction to DNA methylation is given including an overview on biological processes involving DNA methylation events.•Epigenetic studies on events affecting single genes and promoters in the production of biopharmaceuticals are described.•An overview on genome-wide studies of epigenetic phenomena in CHO cells is given.•The outlook highlights important future directions.

Chinese hamster ovary (CHO) cells account for the production of the majority of biopharmaceutical molecules − however, the molecular basis for their versatile properties is not entirely understood yet and the underlying cellular processes need to be characterized in detail. One such process that is supposed to contribute significantly to CHO cell phenotype is methylation of DNA at cytosine residues. DNA methylation was shown to be involved in several central biological processes in humans and to contribute to diseases like cancer. Early studies of DNA methylation in CHO mostly focused on methylation of single recombinant genes and promoters and proved a correlation between DNA methylation status and recombinant gene expression or production stability. More recent publications utilized the CHO genomic and transcriptomic data available since 2011 and provided first insights into the CHO DNA methylation landscape and DNA methylation changes in response to effector molecules or culture conditions. Generally, further genome-wide studies of DNA methylation in CHO will be required to shed light on the relevance of this process regarding biopharmaceuticals production and might, e.g., address a potential link between CHO cell metabolism and DNA methylation or provide novel targets for rational cell line engineering.